Transplant research: Paving the way for a perfect match

Sarah and John Paul Pastore

Sarah Pastore was born with bright blue eyes, a beautiful smile and a single, failing kidney. She fared well in her first few months, but by the time she approached her first birthday her prognosis was clear: without a kidney transplant the little girl from North Reading, Mass., was sure to die.

Her parents, Nancy and Robert, were screened to see if they could be potential donors, but neither was a good match. Because Sarah’s brother John Paul is under 18, he wasn’t eligible to donate. It looked like the next stop was the organ donor list.

But before her name could be submitted to the list, her uncle, Anthony Pastore, was tested to see if he and his niece would be compatible for transplant. As luck would have it, they were, and the 32-year-old Woburn man quickly offered one of his kidneys to save her.

With the live donor identified, Sarah was well on her way to better health. But how exactly do doctors fit an adult kidney in a toddler’s body?

William Harmon, MD

“The human abdomen is capable of a lot of stretching, like when a woman becomes pregnant, or you feel the need to loosen your belt after a big meal,” says William Harmon, MD, chief of Nephrology at Boston Children’s Hospital. “Space isn’t a serious issue for adult-to-child kidney transplants, because an adult sized kidney is only about the size of a fist. It doesn’t take up a lot of volume.”

As long as a child’s renal artery and vein are large enough to provide the transplanted kidney with proper blood flow—which usually happens once the child weighs around 14.5 lbs—adult-to-child kidney transplants are possible. But even after the child has grown large enough, and a donor kidney has been located and successfully transplanted, there can still be complications. When a new organ is transplanted into the body, there is the chance the patient’s immune system will see it as a threat and attack it. If the attack is strong enough it can cause the transplanted kidney to fail. It’s a process known as rejection, and it has complicated the care of transplant patients for decades.

To protect against rejection, transplant recipients are placed on a strict medication plan, often taking several drugs a day. This regimen keeps the transplanted kidney working, but the drugs can cause a variety of side effects that are difficult to deal with, especially for children.

For example, steroids are a common anti-rejection medication, but they can stunt growth and cause weight gain or severe acne. Cyclosporine, another widely used anti-rejection drug, can cause headaches, nausea, tingling fingers and toes, achy joints and unwanted facial hair growth. Many anti-rejection drugs have also been linked to kidney damage, a particular problem for a kidney that’s just been transplanted.

To address the problem, Harmon began looking for medications that would reduce kidney transplant rejections, but do it with fewer long-term side effects. About a decade ago his search directed him to Campath, a strong antibody originally used to fight lymphomas and stop rejection in bone marrow transplants.

Campath works by directly targeting and destroying a person’s lymphocytes, the white blood cells made by the immune system to attack foreign tissue in the body. It then prevents the body from producing new lymphocytes – until the new organ is in place.

“We had experience with a few other methods for temporarily eliminating lymphocytes in the past, but the results were inconsistent,” Harmon says. “Campath works well on a much more consistent basis. One dose and all the lymphocytes are gone for months.”

Three to six months after Campath is administered, the immune system begins to rebound, making new lymphocytes to replace the ones that were destroyed. But the new lymphocytes are different; having never known life before the implanted organ, they don’t see it as foreign. Instead of attacking the new tissue, they ignore it.

“As doctors, our ultimate goal has always been to make life as normal as possible for kids who receive kidney transplants.”

Campath’s effectiveness and lack of side effects has revolutionized bone marrow transplants and the treatment of pediatric lymphoma, but until Harmon’s research, no one had used it for young kidney transplant patients. After years of careful research Harmon was confident that giving the drug to a patient like Sarah would greatly improve her life, and continue to do so for years to come.

“As doctors, our ultimate goal has always been to make life as normal as possible for kids who receive kidney transplants,” he says. “A big part of that is finding ways to reduce the amount of medications they need over time. Thanks to medications like Campath, kids like Sarah are much closer to that goal than ever before.”

The Pastore family couldn’t agree more.

“At first we were nervous about using a treatment that was relatively new for kidney transplant patients, but the confidence we had in Dr. Harmon and the entire staff at Children’s put our minds at ease,” Nancy says. “Now that Sarah is only taking two medicines, instead of seven or eight, we know we made the right decision.”

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